tbuckley/cabot-search huggingface dataset:
Abstract 10291: Elevated C-Reactive Protein Level Amplifies the Association of Lipoprotein(a) With Cardiovascular Risk and Risk Reduction With Alirocumab After Acute Coronary Syndrome
Authors: Gregory G Schwartz, Michael Szarek, Deepak Bhatt, Vera A Bittner, Rafael Diaz, Genevive Garon, Shaun G Goodman, Robert A Harrington, J Wouter W Jukema, Garen Manvelian, Robert Pordy, Harvey D White, Andreas M Zeiher, Philippe G Steg
Journal: Circulation (2022)

Background: In the ODYSSEY OUTCOMES trial (NCT01663402) the PCSK9 inhibitor alirocumab [ALI] reduced the risk of cardiovascular events [CVE] after acute coronary syndrome [ACS] in patients [pts] with elevated atherogenic lipoproteins despite optimized statin treatment, an effect modified by baseline levels of lipoprotein [Lp](a). Levels of the inflammatory biomarker high-sensitivity C-reactive protein [hsCRP] are associated with risk after ACS. In this post hoc analysis, we determined whether Lp(a)-associated risk of CVE after ACS and reduction in that risk with ALI are modified by concurrent hsCRP levels. Methods: 18,924 pts were randomized to ALI or placebo [PBO] 1-12 months after ACS and followed for median 2.8 years. Baseline Lp(a) and hsCRP were available in 18,290 pts. CVE [CV death, non-fatal MI, stroke, unstable angina or heart failure hospitalization, ischemia-driven coronary revascularization, peripheral artery events, and venous thromboembolism] were evaluated by baseline quartile of Lp(a) and by hsCRP dichotomized at 0.2 mg/dL. Results: Median (Q1-Q3) baseline Lp(a) was 21.3 (6.7-59.6) mg/dL. In 10,323 pts with baseline hsCRP&lt;0.2 mg/dL ( Fig top ) risk of CVE in the PBO group increased modestly in Lp(a) Q4 (P trend =0.0592). Overall treatment hazard ratio [HR] was 0.91 without significant trend across Lp(a) quartiles. In 7967 pts with baseline hsCRP≥0.2 mg/dL ( Fig bottom ) risk of CVE in the PBO group was elevated and increased across Lp(a) quartiles (P trend &lt;0.0001). Overall treatment HR was 0.82 and decreased across Lp(a) quartiles (P trend =0.0003). Conclusion: Elevated hsCRP amplifies the relationship of Lp(a) with risk of CVE after ACS and the reduction in that risk with alirocumab. Funding: Sanofi, Regeneron Pharmaceuticals
Abstract 10572: Awareness and Feasibility of Women Chairing Cardiology Sessions in Scientific Meetings: A Nationwide Survey by the Japanese Circulation Society
Authors: Atsuko Nakayama, Chizuko A Kamiya, Sachiko Kanki, Tomomi Ide, Yasuko K Bando, Yukari Uemura, Yayoi T Tsukada
Journal: Circulation (2022)

Introduction: Diversity and inclusion remain a concern in the field of cardiology. Female cardiologists have less opportunity to chair sessions in scientific meetings than men. However, cardiologists’ awareness and perspectives on feasibility of chairing sessions is poorly understood. Methods: A web-based survey on awareness regarding the commitment of chairing sessions was sent to 14,798 certificated cardiologists registered with the Japanese Circulation Society (JCS). Results: A total of 3,412 valid responses were obtained, including 523 women and 2,889 men. Female cardiologists exhibited less interest in serving as chairpersons in Japanese and English sessions (71% women vs. 82% men, P&lt;0.001, 30% women vs. 40% men, P&lt;0.001). Influencing factors of chair acceptance in Japanese sessions for female cardiologists were being a cardiologist for over 10 years (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.02-3.33), experience studying abroad (OR 3.35, 95%CI 1.93-5.81) and chairing sessions (OR 8.39, 95%CI 5.48-12.9), having a Doctor of Philosophy (OR 2.82, 95%CI 1.09-7.31), presence of four or more female cardiovascular specialists in the hospital (OR 1.70, 95%CI 1.10-2.61) and of role models (OR 2.86, 95%CI 1.93-4.24), and awareness of the JCS chairperson’s manual (OR 10.7, 95%CI 6.67-17.1). The receiver operating characteristic curve revealed that the number of female cardiovascular specialists in a hospital was a more sensitive predictor of chair acceptance among male than female cardiologists. Conclusions: Female cardiologists were less likely to accept chairing sessions compared with male cardiologists and the presence of female cardiovascular specialists positively influenced chair acceptance.
Abstract 10940: Cardiovascular Magnetic Resonance Imaging Patterns of Acute Covid-19 Vaccine Associated Myocarditis in Young Male Patients
Authors: Ruben Evertz, Alexander Schulz, Torben Lange, Soeren J Backhaus, Dirk Vollmann, Johannes Kowallick, Stephan von Haehling, Gerd Hasenfuss, Andreas Schuster
Journal: Circulation (2022)

Introduction: The risk of myocarditis after mRNA vaccination against COVID-19 has emerged, recently. Current evidence suggests that young male patients are predominantly affected. In the majority of the cases only mild symptoms were observed. However, little is known about mRNA vaccination related myocarditis cardiac magnetic resonance (CMR) imaging patterns and their differences to classical viral myocarditis in the acute phase of inflammation. Methods: 10 mRNA vaccination associated myocarditis patients were retrospectively enrolled in this study and compared to 10 patients suffering from viral myocarditis, matched with age, sex, comorbidities and laboratory markers. All patients (n = 20) were hospitalized and underwent a standardized clinical examination as well as an echocardiography and a CMR. Both, clinical and imaging findings were compared between both groups. Results: All patients described chest pain as the leading reason for their initial presentation. CMR volumetric and functional parameters did not differ significantly between both groups. In all cases the lateral left ventricular wall showed late gadolinium enhancement without significant differences in terms of the localisation or in-depth tissue characterization. Conclusions: COVID-19 mRNA vaccination associated myocarditis does not show specific CMR patterns during the very acute stage in the most affected patient group of young male patients. The observed imaging markers are closely related with regular viral myocarditis and did not yield any evidence implying adverse outcomes in the investigated patient group.
Abstract 10121: Hypoimmunogenic Human Induced Pluripotent Stem Cells Derived Cardiomyocytes for Cardiac Regeneration
Authors: Yen-Wen Liu, I-Hsien Fang, Saprina P Wang
Journal: Circulation (2022)

Introduction: Post-transplant rejection resulting from human leukocyte antigen (HLA) mismatch is a challenge in allogeneic cell therapy. Human amniotic fluid stem cell-derived iPSCs (hAFSC-iPSCs) are proved to have immune privilege. Hypothesis: hAFSC-iPSC derived cardiomyocytes (hAFSC-iPSC-CMs) are less immunogenic. Methods and Results: hAFSC-iPSCs and hAFSC-iPSC-CMs expressed classical HLA-Ia (HLA-A, -B and -C) and non-classical HLA-Ib but did not have HLA-II expression, indicating that these cells may not be highly immunogenic. We did T Cell Assays to confirm low immunogenicity of hAFSC-iPSC-CMs. We did ischemia-reperfusion surgery of left anterior descending coronary artery to create large transmural myocardial infarction in rats. At post-infarct 4 days, we injected human pluripotent stem cell-derived cardiomyocytes (1.0х10 7 cells/kg), including human embryonic stem cell-derived cardiomyocytes (hESC-CMs), hiPSC-CMs and hAFSC-iPSC-CMs, into the infarcted myocardium. Using very low dose of cyclosporine A (CsA, 2.5 mg/kg/day), only hAFSC-iPSC-CMs transplantation could improve post-infarct cardiac function (left ventricular ejection fraction improvement in hAFSC-iPSC-CMs, hESC-CMs and hiPSC-CMs: 13.1 ± 1.8%, 0.6 ± 1.7% and -1.9 ± 1.6%, respectively). Compared with hESC-CMs and hiPSC-CMs, hAFSC-iPSC-CM transplantation remuscularized the infarcted myocardium with infarct size reduction. Using very low dose CsA, these engrafted hAFSC-iPSC-CMs resulted in a 3-month survival in vivo. hAFSC-iPSC-CMs expressing non-classical HLA-Ib evaded detection and attack by natural killer (NK) cells and cytotoxic T cells because these hAFSC-iPSC-CMs activated the protein tyrosine phosphatase SHP-1/SHP-2 signalling pathway of NK cells and cytotoxic T cells which downregulated signal transducer and activator of transcription 1 (STAT-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression. Conclusions: We demonstrated the immune privilege of hAFSC-iPSC-CM for cardiac regeneration. HLA-Ib-expressing hiPSCs with reduced HLA-II expression are less immunogenic and may serve as platforms for regenerative medicine.
Abstract 10855: Murine Model of Phenylhydrazine-Induced Chronic Hemolytic Anemia Leads to Development of Early Pulmonary Hypertension
Authors: Janae Gonzales, Cat Humpal, Weiguo CHEN, Yulia Epshtein, Dustin R Fraidenburg
Journal: Circulation (2022)

Introduction: Pulmonary hypertension (PH) in sickle cell disease is associated with high morbidity and early mortality, yet the pathogenesis remains incompletely understood. In vitro data by our group implicates extracellular hemoglobin in the endothelial dysfunction that leads to precapillary vascular changes seen in PH and identifies endothelial to mesenchymal transition (EndoMT) as a likely mechanism. To support these findings, we hypothesize that a murine model of chronic hemolysis will show signs of EndoMT and early development of PH. Methods C57BL/6J mice were treated with 40 mg/kg of phenylhydrazine (PHZ), a toxin known to induce hemolysis, or saline, as control, twice a week for three weeks. Plasma cytokine concentrations and complete blood counts were measured. Non-invasive and invasive measures of PH were obtained by echocardiography (TTE), hemodynamic pressure assessments, and measures of right ventricular (RV) hypertrophy. Explanted lung tissue was homogenized and subjected to Western blot analysis to evaluate markers of EndoMT. Results PHZ administration causes anemia (9.1 g/dL vs 11.4 g/dL in control mice) without a significant drop in other hematopoietic cell lines. PHZ-treated mice have increased plasma cytokines CXCL1 and IL-6, which are known to be upregulated in PH. TTE shows significantly decreased pulmonary artery acceleration time (16.7 vs 19.5 msec, p &lt; 0.05), and a trend toward decreased tricuspid annular plane systolic excursion in PHZ-treated mice (0.9 vs 1.2 mm). Invasive hemodynamics show a slight increase in right ventricular systolic pressure (25.6 vs 23.4 mm Hg) and analysis of RV hypertrophy shows increased Fulton index in PHZ-treated mice compared to control (0.28 vs 0.24). Western blot analysis of lung tissue shows upregulation of EndoMT transcription factor SNAI2 in PHZ-treated mice versus control. Conclusions PHZ-treated mice demonstrate early invasive and non-invasive signs of PH with upregulation of EndoMT transcription factor SNAI2, suggesting a relationship between hemolysis, EndoMT, and the development of PH. PHZ administration may be a novel murine model for PH due to chronic hemolysis, facilitating pathobiological and therapeutic discovery for this devastating complication of sickle cell disease.
Abstract 10254: Renal CD11c <sup>+</sup> F4/80 <sup>-</sup> Dendritic Cells, but Not Renal CD11c <sup>+</sup> F4/80 <sup>+</sup> Macrophages, Transfer the Hypertension From Angiotensin II-mice
Authors: Patricio A Araos, Sut'yam Cortes, Rafael Campos, Javier Reyes, Stefanny Figueroa, Maria Jose Fuenzalida, Rodrigo Pacheco, Cristian A Amador
Journal: Circulation (2022)

Introduction: Immune system participates in Angiotensin II (AngII)-hypertension (HTN). Previously, it was shown that dendritic cells (DCs)-CD11c + are required for HTN development. However, new CD11c + cell subpopulations, presenting macrophages (Mφ) characteristics (F4/80 + ), have been described. Since renal DCs and Mφ share several markers, their participation in AngII-HTN remains under discussion. Our objective was to analyze whether renal DCs-CD11c + F4/80 - or/and CD11c + F4/80 + (Mφ) modify their phenotype in the AngII-HTN, and to determine if they promote HTN by transferring this phenotype to normotensive animals. Methods: Male C57BI/6 mice (8-10 weeks-old, n=6) were infused with AngII (490 ng/kg/min) by 14-days. We measured systolic blood pressure (SBP), and renal DCs-CD11c + F4/80 - and Mφ-CD11c + F4/80 + infiltrations were evaluated by flow cytometry. In addition, these cells were isolated at 14-days and transferred to normotensive mice (n=4-5) for SBP measurements. Finally, renal Mφ-CD11c + F4/80 + from HTN mice were stimulated in vitro with AngII (100nM-24h) to analyze the mRNAs abundance of Nox2 , Sgk1 , ENaC and AT 1 R , by qRT-PCR. Results: AngII increased SBP (AngII 134.7±6.9 vs. Vehicle (Vh) 114.5±7.8mmHg; p&lt;0.001) and promoted the infiltration of DCs-CD11c + F4/80 - (AngII=45.6±11.9% vs. Vh=31.7±6.7%; p&lt;0.05) and Mφ-CD11c + F4/80 + (AngII=66.1±8.4% vs. Vh=55.6±5.1%; p&lt;0.05) in renal medulla. No statistical differences we observed in the renal cortex. Interestingly, the adoptive transfer of renal Mφ-CD11c + F4/80 + (1x10 6 -cells) from AngII animals to healthy recipient mice did not transfer HTN after 24h (baseline=106.8.0±2.3 vs. 112.4±4.5mmHg; ns), compared to DCs-CD11c + F4/80 - (baseline=110.0±8.3 vs. 132.0±14.3mmHg; p&lt;0.05). Finally, renal Mφ-CD11c + -F4/80 + purified from HTN animals and re-stimulated in vitro with AngII did not show changes in the mRNA levels evaluated (p&gt;0.05). Conclusions: The AngII-HTN promotes a differentiated infiltration of DCs-CD11c + F4/80 - and Mφ-CD11c + F4/80 + in renal medulla. However, only renal DCs, and not renal Mφ, acquire the ability to transfer HTN, suggesting that renal CD11c + cell subpopulations may have a differential role in AngII-HTN.Supported by Fondecyt-ANID #1201251 and #3201016
Abstract 10566: Hypothermia as an Adjunctive Therapy to Percutaneous Intervention in St-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Control Trials
Authors: Mohammed Mhanna, Meghana Ranabothu, Azizullah Beran, Ahmad Al-Abdouh, Ahmad Jabri, Omar Sajdeya, mahmoud Barbarawi, Ahmad Al-Aaraj, Ehab Eltahawy
Journal: Circulation (2022)

Introduction: In the setting of acute ST-elevation myocardial infarction (STEMI), several randomized control trials (RCTs) suggested a potential benefit with the use of Therapeutic hypothermia (TH). However, results from previous studies are contradictory. Method: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared to the standard percutaneous coronary intervention (PCI) in awake patients with STEMI. The primary outcome was the infarct size (IS) and microvascular obstruction (MVO) assessed by cardiac imaging at the end of follow-up. The secondary outcomes were major adverse cardiovascular events (MACE), procedure-related complications, and door to balloon time. Relative risk (RR) or the mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. Results: A total of 10 RCTs, including 706 patients (mean age: 58±9.6 years, 364 patients managed with adjunctive TH vs. 342 with standard PCI), were included. As compared to standard PCI, TH was not associated with a statistically significant improvement in the IS (MD: -0.87 %, 95%CI: -2.97, 1.23; P = 0.42) or in the MVO (MD: 0.11 %, 95%CI: -0.06, 0.27; P = 0.21). MACE and its individual components were comparable between the two groups. However, the TH approach was associated with an increased risk of infection and prolonged door to balloon time. Furthermore, there was a trend in the TH group toward an increased incidence of stent thrombosis and paroxysmal atrial fibrillation. Conclusions: According to our meta-analysis of published RCTs, the benefit of TH in STEMI patients is modest, with a marginal safety profile and potential for care delays. Larger-scale RCTs are needed to further clarify our results.
Abstract 10248: Incidence and Case-Fatality Rate of Stroke in Argentina: The EstEPA Population Study
Authors: Sebastian F Ameriso, Matias J Alet, Virginia A Pujol Lereis, Mario O Melcon
Journal: Circulation (2022)

Introduction: Stroke epidemiology varies among different populations. The burden of stroke is high in low- and middle-income countries. Reliable population data is needed to assess the impact of stroke and to develop policies aimed to improve stroke care in our region. Objectives: EstEPA is a population-based project assessing prevalence, incidence, mortality and burden of stroke in General Villegas, Buenos Aires, Argentina (pop=30,864 inhabitants). We determined incidence of stroke (first-ever and recurrent stroke) and stroke case-fatality rate from 2017 to 2020. Methods: First-ever strokes, recurrent strokes and transient ischemic attacks were ascertained and case-fatality rate was obtained. Diagnoses were based on standard AHA/WHO definitions. Study population included all persons residing in General Villegas in the three-year period. Hospitals, households, nursing homes, death certificates and several overlapping sources were surveyed. Results: We assessed 92,592 person-years. There were 155 cerebrovascular events, of which 115 were first-ever strokes (74%), 21 recurrent strokes (13·5%) and 19 transient ischemic attacks (12·5%). The annual crude incidence rate of first-ever strokes was 124·2 per 100,000 person-years, while it was 109·7 per 100,000 (95% CI 89·7-129·8), 72·4 per 100,000 (95% CI 47·8-97·0) and 86·9 per 100,000 (95% CI 58·5-115·2) when standardized by the Argentine population, Segi's World population and WHO World population, respectively. The crude incidence rate according to the different subtypes of stroke was 93·4 per 100,000 person-years for ischemic stroke, 18·4 per 100,000 person-years for hemorrhagic stroke and 10·8 per 100,000 person-years for subarachnoid hemorrhage. Incidence increased after age 70. Case fatality rate at 30 days of first-ever strokes was 19·4%. Conclusions: In this first population-based comprehensive stroke epidemiological study in Argentina, first-ever stroke incidence in an urban population was 124·2 per 100,000 person-years. This is lower than the incidence in other countries in the region. It is similar to reported incidence in Western developed countries. Stroke case-fatality rate was comparable to other population-based Latin-American studies and most developed countries.
Abstract 03: Early Post-Cardiac Arrest Blood Pressure Thresholds Associated with Outcomes: A Secondary Analysis of the ICU-Resuscitation Trial
Authors: Monique M Gardner, David Hehir, Ron Reeder, Robert A Berg, Ericka L Fink, Stuart Friess, Kathryn Graham, Monica L Harding, Ryan W Morgan, Vinay M Nadkarni, Heather A Wolfe, Robert M Sutton, Alexis A Topjian
Journal: Circulation (2022)

Introduction: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that maintaining BPs greater than the newly identified post-arrest systolic and diastolic BP thresholds early after IHCA are associated with higher rates of survival to hospital discharge. Methods: We performed a secondary analysis of prospectively collected BP data from the first six hours following index IHCA events enrolled in the ICU-Resuscitation trial. The lowest documented systolic BP (SBP) and diastolic BP (DBP) 0-6 hours post-arrest were categorized by age-based percentiles. After controlling for illness category and presence of pre-arrest hypotension (systolic or mean arterial blood pressure &lt;5 th percentile-for-age or vasoactive/inotropic requirement), cubic spline analyses were generated exploring the association of lowest post-arrest SBP and DBP with survival to hospital discharge and survival with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). Clinical judgement and visual assessment of the spline curves were used to identify BP thresholds. Logistic regression models accounting for illness category and pre-arrest hypotension examined the associations of these thresholds with outcomes. Results: Among 693 index events with 0-6 hour post-arrest BP data, identified thresholds were: SBP &gt;10 th percentile and DBP &gt;50 th percentile for age. Fifty-one percent (n=352) of subjects had lowest SBP above threshold, 50% (n=346) had DBP above threshold. SBP and DBP above thresholds were each associated with survival to hospital discharge (SBP aRR 1.21; 95% CI 1.10, 1.33; DBP aRR 1.23; 1.12, 1.34) and favorable neurologic outcome (SBP aRR 1.22; 1.10, 1.35; DBP aRR 1.27; 1.15, 1.40) (all p&lt;0.001). Conclusions: These data establish that SBP &gt;10 th percentile-for-age and DBP &gt;50 th percentile-for-age during the first 6 hours post-arrest were associated with higher rates of survival to hospital discharge and favorable neurologic outcome.
Abstract 10574: Disrupted Sleep is Associated With Increased 24-Hour Systolic Blood Pressure Variability in Caregivers
Authors: Soojung Ahn, Jill H Esquivel, Eric M Davis, Misook L Chung, Jennifer M Lobo, Jeongok G Logan
Journal: Circulation (2022)

Introduction. A growing body of research shows an association between caregiving and increased cardiovascular disease (CVD) risk. Blood pressure variability (BPV) is known as a surrogate marker of CVD development. However, BPV in caregivers has rarely been used to assess for CVD risk, especially in relation to psychological and behavioral factors. The purpose of this study was to examine the associations of psychological symptoms (i.e., caregiving burden and depressive symptoms) and sleep quality with 24-hour BPV among caregivers of individuals with chronic illness. Methods. Thirty caregivers (25 female; 27 non-Hispanic white; mean age 62 years) who provided in-home care were recruited from the community in this cross-sectional study. Caregiver demographic data, caregiving stress (Zarit Burden Interview), and depressive symptoms (Patient Health Questionnaire-9) were obtained. Sleep quality (i.e., sleep efficiency, wake after sleep onset, the number of awakenings) was assessed using an actigraph for 7 consecutive days. Systolic and diastolic BPV over 24 hours, while awake (daytime), and while sleeping (night time) were obtained by ambulatory BP monitoring. Pearson's correlations and multiple linear regression were conducted to examine associations of psychological symptoms and sleep quality with BPV. Results. Sleep efficiency was negatively correlated with diastolic BPV while awake ( r = -0.368, p = 0.045). The number of awakenings during sleep was positively correlated with systolic BPV while awake ( r = 0.426, p = 0.019) and diastolic BPV while awake ( r = 0.422, p = 0.020). Caregiving stress and depression were not correlated with BPV. After controlling for age and mean arterial pressure, the number of awakenings was associated with increased systolic BPV over 24 hours ( B = 0.194, p = 0.018) and systolic BPV while awake ( B = 0.280, p = 0.002), respectively. Conclusion. Caregivers’ disrupted sleep represented by frequent awakenings may play a role in increased CVD risk as evidenced by increased BPV. While future large clinical studies should be conducted to confirm these findings, improving sleep quality would need to be considered for CVD prevention strategies for caregivers.